Cheng Ruimin, Gao Sheng, Hu Wei, Liu Yamei, Cao Yuchun
Department of Dermatology, Tongji Hospital, The Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Oncol Lett. 2021 Feb;21(2):81. doi: 10.3892/ol.2020.12342. Epub 2020 Dec 1.
The relationship between nuclear factor I/B (NFIB) and cancer attracts growing research interest. NFIB has diverse and specific roles in tumor progression and invasion. However, the potential effects and functions of this transcription factor in melanoma remain unclear. The present study sought to determine the distinguishing properties of NFIB in melanoma cells. Immunohistochemical examination of the tissues of 15 patients with melanoma indicated that the expression of NFIB was high in melanoma specimens, compared with the benign nevus and normal skin specimens. In addition, the relationship between high NFIB expression and low overall survival rate was assessed. Functional studies demonstrated that NFIB enhanced the malignancy of melanoma, including proliferation, migration and invasion. In addition, NFIB silencing in A375 and A875 cell lines inhibited the process of epithelial-mesenchymal transition (EMT), upregulated E-cadherin and zona occludens-1, but suppressed N-cadherin and vimentin expression. These findings may suggest a new function of NFIB in promoting the migration and invasion of melanoma cells. Therefore, the present study further evaluated the association between NFIB and zinc finger protein E-box binding homeobox-1 (ZEB1) in melanoma. Mechanistic experiments revealed that NFIB exerted its roles during EMT by regulating ZEB1. Overall, the present data indicates that NFIB promotes the malignancy of melanoma, particularly EMT, by modulating the ZEB1 axis, such as ZEB2, ATM and CHK1, which may represent a potential molecular therapeutic target in melanoma.
核因子I/B（NFIB）与癌症之间的关系吸引了越来越多的研究关注。NFIB在肿瘤进展和侵袭中具有多样且特定的作用。然而，这种转录因子在黑色素瘤中的潜在影响和功能仍不清楚。本研究旨在确定NFIB在黑色素瘤细胞中的独特性质。对15例黑色素瘤患者组织进行的免疫组织化学检查表明，与良性痣和正常皮肤标本相比，黑色素瘤标本中NFIB的表达较高。此外，还评估了NFIB高表达与低总生存率之间的关系。功能研究表明，NFIB增强了黑色素瘤的恶性程度，包括增殖、迁移和侵袭。此外，在A375和A875细胞系中沉默NFIB可抑制上皮-间质转化（EMT）过程，上调E-钙黏蛋白和闭合蛋白-1，但抑制N-钙黏蛋白和波形蛋白的表达。这些发现可能提示NFIB在促进黑色素瘤细胞迁移和侵袭方面具有新功能。因此，本研究进一步评估了NFIB与黑色素瘤中锌指蛋白E盒结合同源框-1（ZEB1）之间的关联。机制实验表明，NFIB通过调节ZEB1在EMT过程中发挥作用。总体而言，目前的数据表明，NFIB通过调节ZEB1轴（如ZEB2、ATM和CHK1）促进黑色素瘤的恶性程度，尤其是EMT，这可能代表黑色素瘤潜在的分子治疗靶点。
